PROJECT SUMMARY/ ABSTRACT Inorganic arsenic (As) is a potent carcinogen and toxicant associated with numerous adverse health outcomes, including lung, skin, and bladder cancers and cardiovascular disease (CVD). The Environmental Protection Agency (EPA) regulates As in public drinking water via the Safe Drinking Water Act by setting the maximum contaminant level (MCL) allowable in public water systems. The current MCL (10 g/L, down from 50 g/L) was implemented in 2006. Our preliminary study found a 17% decrease in urine As between NHANES 2003/2004 and NHANES 2013/2014 likely due to reductions in As in drinking water following the implementation of the new MCL. There is a critical need to identify susceptible subgroups whose water As remains high, by geography, race/ethnicity, or socioeconomic status, to inform further interventions. Moreover, there is a critical need to determine if reductions in drinking water As are associated with reductions in As- related disease. In the proposed study, we will determine the association between water As (estimated via the United States Geologic Survey?s updated arsenic map and the EPA?s Six Year Review of Contaminant Occurrence Database) with urine As measured in the National Health and Nutrition Examination Survey (NHANES) and total and cardiovascular mortality from the National Vital Statistics database. Our aims are: (1) Determine the association of estimated census tract- and county-level water As exposure with urinary As levels, (2) Investigate the impact of the implementation of the MCL on changes in water As exposure, and (3) Investigate the impact of changes in water As exposure with temporal trends in county-level total and cardiovascular disease mortality. This proposed study will contribute to our understanding of how national drinking water regulations impact exposure to drinking water As and subsequent As-related disease. We will identify subgroups not adequately protected by the current As MCL and further explore the contribution of As exposure to the ongoing cardiovascular disease epidemic as well as the potential positive impact of As regulation in drinking water in preventing cardiovascular disease. This study combines two national water As databases for surveillance of water As exposure and uses a novel residual-based biomarker to isolate urine water As resulting from drinking water. This study responds directly to NIEHS Strategic Plan goals, including Goal 2 (?Understand individual susceptibility? to chronic, complex diseases resulting from environmental factors?), Goal 6 (?Establish an environmental health disparities research agenda to understand the disproportionate risks of disease, and to define and support public health and prevention solutions in affected populations?), and Goal 10 (?Evaluate the economic impact of policies? that reduce exposure to environmental toxicants, through prevention of disease and disabilities?).